SRP54 is an essential component of the signal recognition particle (SRP) complex that mediates cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) 1. The protein binds to signal sequences of nascent secretory proteins emerging from ribosomes and associates with the SRP receptor subunit SRPRA in a GTP-dependent manner to facilitate protein translocation 1. SRP54 exhibits GTPase activity and stimulates reciprocal GTPase activation of SRPRA, with these enzymatic activities being critical for the targeting mechanism 2. The protein contains a methionine-rich M-domain that binds SRP RNA, and systematic mutagenesis has identified specific amino acid residues (positions 379-387, 394-396, 400-405, and 409-411) essential for RNA binding 2. Disease-wise, heterozygous missense mutations in SRP54 cause severe congenital neutropenia through dominant-negative effects that impair unconventional splicing of transcription factor XBP1 3. These mutations lead to neutrophil maturation defects and can present with symptoms overlapping Shwachman-Diamond syndrome 4. Clinically, SRP54-associated neutropenia requires careful monitoring as patients face increased infection risk and potential myeloid transformation 5.