NHLRC2 (NHL repeat containing 2) is an essential protein required for normal embryonic development 1. Structurally, it comprises thioredoxin-like and NHL repeat β-propeller domains forming a conserved cleft containing a CCINC motif, suggesting a functional binding site 2. NHLRC2 functions as a central regulator of phagocytosis by controlling RhoA-Rac1 signaling cascades that modulate actin polymerization and filopodia formation 3. Additionally, NHLRC2 is required for terminal erythroid differentiation and positively regulates efferocytosis of apoptotic erythrocytes by leptomeningeal lymphatic endothelial cells through phosphatidylserine receptor-mediated mechanisms, contributing to neuroprotection post-subarachnoid hemorrhage 45. Biallelic NHLRC2 mutations cause FINCA disease (fibrosis, neurodegeneration, and cerebral angiomatosis), a multisystem infantile-onset disorder 1. Disease-causing variants enhance myofibroblast differentiation and disrupt cytoskeletal organization and vesicle transport 6. Clinical presentations include severe pulmonary and cardiac fibrosis, neurodevelopmental delay, immunodeficiency with recurrent infections, and macrocytic anemia, though some patients survive beyond infancy 71. The p.Asp148Tyr variant alters Rho GTPase signaling and impairs innate immune responses, particularly interferon-γ production 8. These findings position NHLRC2 as critical for coordinating cellular uptake mechanisms, immune function, and tissue homeostasis.