CRCT1 (cysteine-rich C-terminal 1) is a tumor suppressor gene encoded by the epidermal differentiation complex that regulates cell proliferation and apoptosis across multiple cancer types. In esophageal squamous cell cancer (ESCC), CRCT1 is downregulated in association with TNM stage and lymph node metastasis; restoring CRCT1 expression inhibits cell proliferation, suppresses xenograft tumor formation, and promotes apoptosis through upregulation of apoptosis-related proteins 1. CRCT1 functions as a direct target of microRNA-520g, which inversely correlates with CRCT1 levels in ESCC tissues 1. Beyond ESCC, CRCT1 shows altered expression in HPV-positive oropharyngeal squamous cell carcinomas 2 and is downregulated in cervical cancer 3. Notably, CRCT1 demonstrates significant clinical diagnostic potential as a salivary extracellular RNA biomarker for gingivitis, achieving 71% sensitivity and 100% specificity when included in a four-marker panel (SPRR1A, lnc-TET3-2:1, FAM25A, CRCT1) 4. CRCT1 is also differentially expressed in periodontal ligament tissues during vertical tooth movement 5. Additionally, CRCT1 has been identified in a novel melanocytic tumor fusion event (CRCT1::TRIM11) 6. These findings position CRCT1 as a multi-functional tumor suppressor with potential applications in cancer diagnosis, prognosis, and therapeutic development.