ACVR1C (activin A receptor type 1C) is a type I serine/threonine kinase that functions as a key component of the TGF-β superfamily signaling pathway. As a transmembrane receptor, ACVR1C forms a heteromeric complex with type II receptors upon ligand binding, leading to phosphorylation and activation of SMAD2/3 transcriptional regulators 1. ACVR1C serves as the primary receptor for activin E and nodal ligands, mediating diverse cellular responses including apoptosis, differentiation, and metabolic homeostasis. Mechanistically, ACVR1C activation suppresses PPARG target genes and reduces lipolysis in adipose tissue, promoting fat accumulation and storage 1. Loss of ACVR1C signaling conversely increases lipolysis and fatty acid oxidation, improving metabolic health. In brown adipocytes, ACVR1C activation via activin E upregulates uncoupling protein 1 (UCP1) and fibroblast growth factor 21 (FGF21), enhancing energy expenditure 2. Clinically, human ACVR1C variants associate with altered body fat distribution and metabolic disease risk. Rare loss-of-function variants correlate with lower waist-to-hip ratio and type 2 diabetes protection 3, while specific missense variants produce graded metabolic phenotypes 4. Additionally, ACVR1C bidirectionally regulates synaptic plasticity and long-term memory formation, with reduced expression in aging and Alzheimer's disease models 5. These findings identify ACVR1C as a therapeutic target for obesity, diabetes, and cognitive impairment.