NRG4 (neuregulin 4) is an adipokine and low-affinity ligand for the ERBB4 receptor tyrosine kinase, functioning as a key regulator of metabolic homeostasis and cancer progression through adipose-organ tissue communication. Mechanistically, NRG4 binds ERBB4 and recruits ERBB1 and ERBB2 coreceptors to stimulate tyrosine phosphorylation and downstream signaling 1. The NRG4/ERBB4/AKT pathway suppresses hepatic steatosis by phosphorylating cGAS to inhibit cGAS-STING-mediated inflammation, representing a key mechanism by which exercise ameliorates metabolic dysfunction-associated steatotic liver disease (MASLD) 2. In humans, NRG4 and ERBB4 expression decreases with elevated BMI, correlating inversely with lipogenesis genes like ACACA, suggesting an antilipogenic role 3. Beyond liver metabolism, NRG4 regulates wound healing by promoting subcutaneous white adipose tissue (sWAT) beiging, where beige adipocytes express abundant NRG4 to regulate macrophage polarization and myofibroblast function 4. In breast cancer, NRG4 acts as a metastasis suppressor through ERBB4-YAP1 signaling, suppressing matrix metalloproteinase expression to inhibit EMT and invasion 5. Clinically, plasma ERBB4+ exosomes are independent prognostic factors for breast cancer patients with comorbid NAFLD 1, and NRG4 represents a promising therapeutic target for obesity-associated metabolic and malignant disorders 6.