Cartpt, encoding cocaine-and amphetamine-regulated transcript prepropeptide, is involved in multiple biological processes. It has been linked to pathways related to reward processing, metabolism, and tissue development. In the nucleus accumbens, Cartpt-positive neurons are associated with behavior aversion, indicating its role in reward-related behaviors [2]. In pancreatic beta cells, CART, the peptide encoded by Cartpt, acts through GPR162 to regulate insulin secretion and cytoskeletal arrangement [3].

In a preosteoblast-specific Atrx conditional knockout mouse model, Atrx-deficient osteolineage cells expressed high levels of Cartpt. Mechanistically, ATRX suppresses Cartpt transcription by binding to its promoter. Silencing Cartpt in these cells rescued the molecular phenotype by increasing the Rankl/Opg expression ratio, suggesting Cartpt's role in skeletal development [4]. In human thoracic aortic aneurysm (TAA) samples, a spatially distinct CARTPT-expressing smooth muscle cell (SMC) subtype was identified, especially in male samples. Functional studies showed that human CART promotes the osteochondrogenic switch of aortic SMCs, potentially leading to medial calcification of the thoracic aorta [1].

In summary, Cartpt plays diverse roles in biological processes such as reward processing, metabolism, skeletal development, and vascular homeostasis. Studies using gene knockout or conditional knockout mouse models, like the Atrx-related model, have provided insights into its function in skeletal development. The identification of the CARTPT-expressing SMC subtype in TAA samples also emphasizes its significance in vascular-related diseases.