STRA6, encoded by the stimulated by retinoic acid 6 gene, is a multifunctional membrane protein. It is crucial for the transport of vitamin A (retinol) across cell membranes, acting as a transmembrane pore that enables bidirectional vitamin A transport between extra-and intracellular retinoid binding proteins [2]. This process is coupled with vitamin A esterification for cellular vitamin A accumulation. STRA6 also functions as a ligand-activated cell surface signaling receptor, activating the JAK/STAT signaling pathway upon binding of holo-RBP, leading to the induction of STAT target genes [5].

In a denervation-induced muscle atrophy model, knockout of RBP4, which interacts with STRA6, alleviated fatty infiltration and muscle atrophy, while injection of holo-RBP4 aggregated these conditions. Mechanistically, holo-RBP4 treatment increased STRA6 expression and promoted phosphorylation of downstream JAK2 and STAT3, and inhibition of the STRA6/JAK2/STAT3 pathway could rescue the effects on muscle atrophy markers [1]. In thyroid carcinoma, stable STRA6-knockdown cells showed reduced proliferation and metastasis in vitro and in vivo, and STRA6 was found to interact with integrin-linked kinase (ILK) and activate the AKT/mTOR signaling pathway [3]. In BRAF-mutant papillary thyroid carcinoma, STRA6 was upregulated, predicted unfavorable survival, and was associated with immune infiltrates and T cell exhaustion [4].

In conclusion, STRA6 plays essential roles in vitamin A transport and cell signaling. Through gene-knockout based research in models like mice, its functions in disease conditions such as muscle atrophy and thyroid carcinoma have been revealed. Understanding STRA6 provides insights into the mechanisms of these diseases and may offer potential therapeutic targets.