TM9SF1 (transmembrane 9 superfamily member 1) is a nine-transmembrane domain protein that plays a central role in selective autophagy and cellular homeostasis. Functionally, TM9SF1 acts as an autophagosome-inducing protein 1 that colocalizes with LC3 and increases autophagosome formation; knockdown of TM9SF1 impairs starvation-induced autophagy 1. The protein regulates mTOR-dependent autophagy in B cells, controlling differentiation into antibody-producing plasma cells 2. In non-immune contexts, TM9SF1 facilitates selective autophagic degradation of specific cargo proteins: it promotes K63-linked ubiquitination of Vimentin by TRIM21 for Tollip-mediated degradation in colorectal cancer 3, and drives lipophagy via AMPK-ULK1 signaling in HER2-positive breast cancer 4. Disease relevance is substantial: elevated TM9SF1 expression correlates with autoimmune disease activity (rheumatoid arthritis and systemic lupus erythematosus), outperforming clinical indicators in predicting disease activity 2; conversely, TM9SF1 downregulation in colorectal cancer associates with favorable prognosis 3. In ARDS, increased TM9SF1 predicts severity and mortality 5. Clinically, TM9SF1 represents a promising biomarker for monitoring autoimmune and inflammatory disease activity and predicting cancer prognosis across multiple malignancies 6.