Recurrent mechanisms underlying insulin resistance in PCOS included post-receptor defects in IRS/PI3K/AKT and MAPK signaling, impaired GLUT4 expression and trafficking, mitochondrial and glycolytic dysfunction, chronic low-grade inflammation, androgen receptor-mediated metabolic reprogramming, circadian rhythm disruption, and epigenetic or environmental modulators. The gene discussed is IARS1; the disease is Insulin resistance.