PROTEOSTASIS THERAPEUTICS, INC. NON-EMPLOYEEDIRECTOR COMPENSATION POLICY

Exhibit 10.16

PROTEOSTASIS THERAPEUTICS, INC.

NON-EMPLOYEE DIRECTOR COMPENSATION POLICY

The purpose of this Non-Employee Director Compensation Policy of Proteostasis Therapeutics, Inc. (the “Company”), is to provide a total compensation package that enables the Company to attract and retain, on a long-term basis, high-caliber directors who are not employees or officers of the Company or its subsidiaries. In furtherance of the purpose stated above, all non-employee directors shall be paid compensation for services provided to the Company as set forth below:

Cash Retainers

Annual Retainer for Board Membership: $35,000 for general availability and participation in meetings and conference calls of the Board of Directors, to be paid quarterly. No additional compensation for attending individual Board meetings.

Additional Retainers for Committee Membership:

Note: Chairperson and Committee retainers are in addition to annual board member retainers. No equity retainers shall be paid as compensation for committee membership.

All cash retainers will be paid quarterly, in arrears, or upon the earlier resignation or removal of the non-employee director. Cash retainers payable to non-employee directors are annualized, meaning that non-employee directors who join the Board during the calendar year, and with respect to all non-employee directors for 2015, such amounts shall be pro-rated based on the number of calendar days served by such director from and after the effective date of this Policy.

Each non-employee director shall have the right to elect to receive all or a portion of his or her annual cash retainer under this Policy in the form of stock options to purchase shares of the Company’s common stock (“Elective Grants”). Any such election must be made before the start of the Company’s fiscal year; provided, however (i) a new non-employee director may make such election within ten (10) days of first becoming eligible to receive any cash retainer pursuant

to this Policy and (ii) a current non-employee director may make such election at any time before this Policy becomes effective. Any stock options granted pursuant to this election shall vest in equal tranches at the end of each fiscal quarter following the date of grant, in such amounts such that such stock options would be fully vested at the end of the fiscal year of the date of grant, provided, however, that all vesting ceases if the board member resigns from the Board of Directors or otherwise ceases to serve as a director, unless the Board of Directors determines that the circumstances warrant vesting acceleration. The number of shares underlying the stock options shall be determined by the Company using a Black-Scholes methodology and its customary assumptions therefor, and shall have an exercise price equal to the reported closing price on the date of grant, or the preceding business day if there are no market quotations on such date.

The Elective Grants held by non-employee directors will accelerate and all unvested shares underlying the Elective Grants shall immediately vest upon a Sale Event (as defined in the Company’s 2015 Stock Option and Incentive Plan).

Equity Retainers

Upon initial election to the Board: An initial, one-time equity grant (the “Initial Grant”) with a value of $195,000 of equity awards in the form of stock options and/or restricted stock units, as determined by the Compensation Committee of the Board, to each new non-employee director, that vests quarterly over three years starting on the grant date, provided, however, that all vesting ceases if the board member resigns from the Board of Directors or otherwise ceases to serve as a director, unless the Board of Directors determines that the circumstances warrant vesting acceleration. The number of shares underlying the stock options shall be determined by the Company using a Black-Scholes methodology and its customary assumptions therefor, and shall have an exercise price equal to the reported closing price on the date of grant, or the preceding business day if there are no market quotations on such date. The number of shares underlying the RSU portion of the equity grant shall be based on the actual value of the shares on the date of grant. This initial equity grant applies only to non-employee directors who are first elected to the Board effective as of or subsequent to the Company’s initial public offering.

The Initial Grants held by non-employee directors will accelerate and all unvested shares underlying the Annual Grants shall immediately vest upon a Sale Event (as defined in the Company’s 2016 Stock Option and Incentive Plan).

Annual equity grants: Each continuing non-employee member of the Board who has served as a director for the previous six months will receive, immediately following the Company’s annual meeting of stockholders, an annual equity grant (the “Annual Grant”) with a value of $97,000 of equity awards in the form of stock options and/or restricted stock units, as determined by the Compensation Committee of the Board, that vests quarterly over one year starting on the grant date, provided, however, that all vesting ceases if the director resigns from the Board of Directors or otherwise ceases to serve as a director, unless the Board of Directors determines that the circumstances warrant vesting acceleration. The number of shares underlying the stock options shall be determined by the Company using a Black-Scholes methodology and its customary assumptions therefor, and shall have an exercise price equal to the reported closing price on the date of grant, or the preceding business day if there are no market quotations on such date. The number of shares underlying the RSU portion of the equity grant shall be based on the actual value of the shares on the date of grant.

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The Annual Grants held by non-employee directors will accelerate and all unvested shares underlying the Annual Grants shall immediately vest upon a Sale Event (as defined in the Company’s 2015 Stock Option and Incentive Plan).

Expenses

The Company will reimburse all reasonable out-of-pocket expenses incurred by non-employee directors in attending meetings of the Board or any Committee.

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Adopted by the Board on December 22, 2015, effective as of the effectiveness of the Company’s registration statement on Form S-1.

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