NAA15 encodes a core auxiliary subunit of the NatA (N-alpha-acetyltransferase A) complex, which plays a critical role in co-translational protein acetylation as proteins emerge from the ribosome. Loss of functional NAA15—often through nonsense-mediated decay—reduces effective protein dosage, impairing neuronal differentiation, synaptic connectivity, and cortical network formation.

Clinically, NAA15 haploinsufficiency presents as a neurodevelopmental syndrome characterized by seizures, motor and speech apraxia, sensory processing disorder, heart disease, and variable systemic involvement. In GG’s case, this phenotype is accompanied by immune dysregulation, including elevated ANA and anti-CCP antibodies and Crohn-like gastrointestinal inflammation, suggesting broader neuroimmune crosstalk and cellular stress responses.

This combination of neurological and systemic features positions NAA15 as both a developmental and regulatory gene—making it a compelling candidate for precision therapeutic exploration.