CRTC3 (CREB regulated transcription coactivator 3) is a transcriptional coactivator that functions as a key regulator of CREB-mediated gene expression through the SIK/TORC signaling pathway 1. When dephosphorylated, CRTC3 activates transcription at cAMP response element (CRE) sites independently of CREB phosphorylation status 2. In skeletal muscle and adipose tissue, CRTC3 regulates energy homeostasis by controlling glucose uptake, lipid metabolism, glycogen metabolism, and mitochondrial biogenesis; global CRTC3 knockout enhances energy expenditure and protects against obesity 1. CRTC3 also plays a critical role in melanogenesis by directly targeting microphthalmia-associated transcription factor (MITF) and regulating melanogenesis-related genes; CRTC3-null mice display reduced melanin deposition 2. In intestinal epithelial cells, CRTC3 regulates tight junction protein expression including ZO-1, ZO-2, occludin, and claudin-1 3. Clinically, dysregulation of CRTC3 has pathological significance: in melanoma, dasatinib activates a CRTC3/MITF/Bcl-2 pathway causing drug resistance 4, while CRTC3 and related CRTC family members restrict SARS-CoV-2 replication through direct interaction with viral RdRp NSP12 5. Additionally, CRTC3 has been identified as a bipolar disorder risk gene 6, and CRTC3-MAML2 fusions are associated with mucoepidermoid carcinoma of salivary glands 7.