Schematic representation of the mechanism of disease pathogenesis in the patient is shown. Normally, the signal recognition particle (SRP) recognizes the signal peptide upon exiting from the ribosome exit tunnel, which halts translation of the protein until the ribosome–nascent chain complex (RNC) is translocated to the ER membrane. At the ER membrane, SRP binds to the SRP-receptor, and the RNC complex is transferred to the translocon, resuming translation. The translated protein is processed (signal peptide cleavage, protein folding, and post-translational modifications), and the protein is transported to the plasma membrane via the Golgi apparatus. In the patient, the mutation in the signal peptide results in inefficient SRP recognition during translation. SRP recognition protects the mRNA, and failure of signal peptide recognition by SRP triggers regulation of aberrant protein production (RAPP)-mediated mRNA degradation, resulting in reduced and variable IL2RG protein expression in the patient.