PSCA (prostate stem cell antigen) is a GPI-anchored cell surface protein that acts as a modulator of nicotinic acetylcholine receptor activity, inhibiting nicotine-induced signaling through alpha-3:beta-2 and alpha-7 containing nAChRs. 1 identifies PSCA as a marker of stemlike luminal cells in the prostate that contribute to gland regeneration following androgen restoration, alongside differentiated populations. PSCA expression is functionally relevant across multiple disease contexts. Genetic variants in PSCA are associated with susceptibility to peptic ulcer disease, 2 likely through roles in Helicobacter pylori infection response and gastric acid regulation. 3 and 4 establish that PSCA genetic variations and upregulated expression contribute to gastric cancer risk, particularly diffuse-type tumors, with upregulated PSCA expression identified as a plausible pathomechanism at gastric cancer GWAS loci. Clinically, PSCA represents a validated immunotherapy target. 5 highlights PSCA among treatment-resistant prostate cancer surfaceome targets for therapeutic exploitation. 6 and 7 demonstrate clinical feasibility of PSCA-directed CAR T cell therapies in metastatic castration-resistant prostate cancer and pancreatic cancer, with patients achieving prostate-specific antigen declines and radiographic improvements, though durability remains limited. 8 shows CAR macrophages targeting PSCA exhibit potent antitumor activity against pancreatic cancer, supporting alternative cellular immunotherapy platforms for solid tumors.