CREB-regulated transcription coactivator 2 (CRTC2)

CREB-regulated transcription coactivator 2 (CRTC2) is a scaffold protein that binds to CREB, amplifying the transcriptional response of genes regulated by cAMP and calcium signaling[1][2][3][5]. CRTC2 is crucial for metabolic regulation, especially glucose and lipid metabolism; it orchestrates hepatic gluconeogenesis during fasting and modulates cholesterol synthesis and autophagy[1]. CRTC2 does not bind DNA directly but is recruited to promoters through CREB, playing key roles in transcriptional coactivation[3]. Dysregulation of CRTC2 is implicated in metabolic disorders (diabetes, obesity), cardiovascular disease (atherosclerosis), and cancer biology (especially in STK11/LKB1-deficient lung cancer)[1][2]. Pathways impacting CRTC2 activity—including phosphorylation, glycosylation, and nuclear translocation—may serve as therapeutic entry points, although no drugs directly targeting CRTC2 are current clinical standard[1][2][5].

Other names

CRTC2TORC2Transducer of regulated cAMP response element-binding protein 2Transducer of CREB protein 2

Drugs or compounds affecting cAMP/PKA pathways (modulate CRTC2 phosphorylation/activation); Modulators of SIK2 or OGT (glycosylation/phosphorylation status impacts nuclear translocation and activity); Agents influencing CREB activity or SREBP signaling may indirectly affect CRTC2 function