SGSM1 (small G protein signaling modulator 1) is a RUN and TBC domain-containing protein that functions as a modulator of Rab and Rap small GTPase-mediated signaling. SGSM1 acts as both a GTPase-activating protein for RAB34 and RAB36, and as an effector protein for RAB9A and RAB9B, localizing to the trans-Golgi network and cytoplasm where it regulates vesicular transport and neuronal signaling 1. The protein is primarily expressed in brain, heart, and testis tissues 1. Disease relevance spans multiple cancer types. In nasopharyngeal carcinoma, SGSM1 degradation via the SHISA3-TRIM21 axis promotes cell invasion and metastasis through MAPK pathway activation 2. In lower-grade gliomas, low SGSM1 expression independently predicts poor overall survival and correlates with reduced immune infiltration 3. Pan-cancer analysis reveals SGSM1 downregulation across multiple malignancies (HNSC, COAD, BRCA, KIRP, KIRC, MESO, PAAD, UCEC), with prognostic significance particularly in renal and pancreatic cancers 45. SGSM1 is implicated in the tumor immune microenvironment and represents a potential therapeutic target. Additionally, SGSM1 has been identified as a hub gene in amyotrophic lateral sclerosis and depression 6, and is a candidate schwannomatosis-predisposing gene 7.