USP38 and cancer: Future research must prioritize (1): Deep mechanistic studies elucidating both upstream regulatory inputs and downstream effector pathways in diverse, physiologically relevant models (including in vivo systems) (2); Systematic investigation of USP38’s role in resistance to various anti-cancer therapies across multiple tumor types (3); Detailed structural and functional characterization of USP38, including mapping all potential catalytic sites and substrate interaction interfaces; and (4) Rigorous preclinical validation of USP38 inhibitors, both as monotherapy and in combination regimens.