USP8

USP8 encodes ubiquitin-specific protease 8, a deubiquitinating enzyme that regulates protein stability by cleaving ubiquitin moieties from target substrates. Key substrates include EGFR, ALK, and endosomal sorting proteins, linking USP8 to receptor tyrosine kinase (RTK) signaling and endocytic trafficking pathways.
Aberrant USP8 activity is associated with Cushing's disease via stabilizing pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1R) in corticotroph adenomas. Emerging preclinical studies explore USP8 inhibitors as potential therapies for RTK-driven cancers and pituitary disorders, though no clinical candidates have advanced to late-stage trials.