INSL4 (insulin-like 4) is a primate-specific member of the insulin/relaxin superfamily with dual roles in placental development and pathological processes. Primarily, INSL4 functions in trophoblast development, where it is predominantly expressed in syncytiotrophoblast cells of the human placenta 1. The gene also regulates bone formation, with expression detected in the perichondrium and interbone ligaments of embryonic skeletal tissues 1. INSL4 expression is mediated by a human endogenous retrovirus (HERV) element in its promoter, enabling placenta-specific regulation during cytotrophoblast differentiation 2. Mechanistically, INSL4 is translated into pro-EPIL and mature EPIL peptides that signal through insulin-like growth factor receptors 3. Dysregulation of INSL4 has emerged as clinically significant in lung cancer pathogenesis. In LKB1-inactivated non-small cell lung cancer (NSCLC), INSL4 is aberrantly induced through CRTC-CREB signaling and sustains tumor growth and survival 4. High INSL4 expression correlates with advanced tumor stage, lymph node metastasis, and worse overall survival 4. Conversely, in fetal growth restriction, INSL4 expression is downregulated in dysfunctional placentas and is regulated by SIRT1, suggesting the SIRT1-INSL4 axis represents a therapeutic target 5.