TCAF1 (TRPM8 channel-associated factor 1) is a regulatory protein that functions as a positive regulator of ion channel activity and cellular stress responses. Mechanistically, TCAF1 promotes the trafficking of TRPM8 to the cell surface and facilitates TRPV2-mediated calcium release by dissociating STING from TRPV2, thereby relieving channel repression 12. This TRPV2-mediated calcium signaling is essential for replication fork protection, chr7 stability, and cell survival under replication stress conditions 2. Clinically, TCAF1 demonstrates dual relevance in cancer biology. In prostate cancer, TCAF1 expression reduces cell migration speed and directionality, with loss of TCAF1 observed in metastatic specimens, suggesting a tumor-suppressive role 1. Consistently, hypermethylation of the RHCG-TCAF1 promoter panel independently predicts biochemical recurrence in prostate cancer patients treated with radical prostatectomy, adding prognostic value beyond established parameters 3. In pancreatic adenocarcinoma, elevated TCAF1/TCAF2 expression correlates with tumor stage and metastasis-associated gene expression, indicating potential oncogenic roles 4. Evolutionary evidence indicates human-specific TCAF duplications arose ~1.7 million years ago and underwent diversification potentially in response to cold or dietary adaptations 5.