SLC2A4 encodes GLUT4, an insulin-regulated glucose transporter essential for glucose homeostasis and metabolic health. In the basal state, GLUT4 is sequestered intracellularly within storage compartments in muscle and adipose tissue 1. Upon insulin stimulation, GLUT4 translocates to the plasma membrane via a signaling cascade involving AMPK, Ca²⁺, GTPases, and SNARE proteins, enabling glucose uptake by facilitated diffusion 1. Exercise similarly promotes GLUT4 translocation through contraction-induced signaling distinct from insulin pathways, while also increasing GLUT4 expression via the HDAC4/5-MEF2 axis 1. SLC2A4 dysfunction is implicated in type 2 diabetes mellitus (T2DM), with multiple genetic variants associated with T2DM risk and insulin resistance 2. In obesity, SLC2A4 expression is suppressed through increased DNA methylation in enhancer regions, correlating with impaired insulin sensitivity and de novo lipogenesis in visceral adipose tissue 3. Physical inactivity reduces muscle GLUT4 expression, contributing to decreased glucose uptake and T2DM pathogenesis 4. GLUT4 dysfunction in adipose tissue impairs lipid storage capacity and insulin sensitivity, promoting ectopic fat accumulation and metabolic syndrome 5.