TFCP2L1 is a transcription factor critical for maintaining pluripotency and self-renewal in embryonic stem cells (ESCs). In mouse ESCs, TFCP2L1 directly induces estrogen-related receptor β (Esrrb) expression to support ESC identity 1, while in human ESCs it selectively enhances Kruppel-like factor 4 (Klf4) expression to promote self-renewal 1. TFCP2L1 functions as a major effector of self-renewal downstream of LIF/STAT3 and Wnt/β-catenin signaling 2. Beyond pluripotency, TFCP2L1 regulates kidney collecting duct development and coordinates intercalated cell differentiation by regulating V-ATPase subunits, CA12, and FOXI1 expression. In cancer contexts, TFCP2L1 exhibits context-dependent roles. In thyroid cancer, TFCP2L1 acts as a tumor suppressor—its downregulation correlates with malignant characteristics and poor prognosis, while overexpression inhibits cell growth and motility through NF-κB pathway inactivation 3. Conversely, in renal medullary carcinoma, TFCP2L1 loss and MYC gain promote oncogenic transformation and ferroptosis resistance 4. TFCP2L1 also modulates placental CYP11A1 expression. These findings establish TFCP2L1 as a multifunctional transcriptional regulator with important roles in developmental biology and cancer progression.