SOS2 (SOS Ras/Rho guanine nucleotide exchange factor 2) functions as a guanine nucleotide exchange factor that catalyzes GDP-to-GTP exchange in RAS proteins, particularly HRAS, thereby activating RAS signaling pathways 1. The protein acts as a key modulator of PI3K-AKT signaling and plays essential roles in cellular signaling cascades. SOS2 demonstrates both functional redundancy and specificity compared to its homolog SOS1, with evidence suggesting SOS2 has specific functions in keratinocyte regulation and epidermal stem cell homeostasis 2. Disease-wise, pathogenic variants in SOS2 are associated with Noonan syndrome, a RASopathy characterized by multisystemic developmental abnormalities 3. Patients with SOS2 mutations show particularly high prevalence of lymphatic anomalies during infancy and childhood, including increased nuchal translucency, chylothorax, and lymphedema 4. Additionally, SOS2 variants have been identified in male infertility cases, especially those with cryptorchidism and spermatogenic failure 5. Clinically, SOS2 represents a therapeutic target, as concurrent SOS1 and MEK inhibition shows promise in treating NF1-null melanomas, exploiting reduced SOS activity in these tumor cells 6. SOS2 variants are also associated with kidney function abnormalities and growth hormone insensitivity syndromes 78.