FCHO1 (FCH and mu domain containing endocytic adaptor 1) functions as a critical early-stage regulator of clathrin-mediated endocytosis (CME), playing essential roles in immune cell development and function 1. The protein acts as a membrane-binding component that nucleates clathrin-coated pit formation and recruits essential proteins for functional endocytic vesicle assembly 2. FCHO1's μ-homology domain serves as an endocytic interaction hub, enabling cargo recognition and signal modulation 2. In T cells, FCHO1 is crucial for T cell receptor (TCR) clustering, internalization, and subsequent activation, with deficiency leading to impaired T cell responsiveness 1. Human FCHO1 deficiency causes severe combined immunodeficiency characterized by recurrent sinopulmonary, viral, and fungal infections, lymphopenia (particularly CD4+ T cell depletion), hypogammaglobulinemia, and increased susceptibility to neurological disorders and malignancies including B cell lymphomas 3. The protein also regulates BMP signaling through receptor endocytosis during developmental patterning 2. FCHO1 mutations disrupt protein localization and binding partner interactions, resulting in defective clathrin-coated pit formation 1. Clinically, allogeneic hematopoietic stem cell transplantation has emerged as a curative treatment for FCHO1 deficiency patients 3.