ATP5PD encodes the peripheral stalk subunit d of mitochondrial ATP synthase (Complex V), a critical component of the F₀F₁-ATP synthase complex 1. This subunit functions as part of the stationary peripheral stalk that acts as a stator, holding the catalytic α₃β₃ core and subunit a static relative to rotating central stalk elements 1. During oxidative phosphorylation, ATP5PD enables coupling of proton translocation across the inner mitochondrial membrane to ATP synthesis through a rotary catalytic mechanism 1. Clinically, ATP5PD dysfunction is emerging as relevant to multiple diseases. Proteomic analysis of autoimmune-related kidney diseases identified ATP5PD among significantly altered mitochondrial proteins in tubular tissues, implicating mitochondrial dysfunction in kidney damage pathways 2. In HIV-1-infected macrophages exposed to cocaine, ATP5PD upregulation by the sigma-1 receptor antagonist BD1047 protects against mitochondrial damage and neurotoxicity 3. Variants in ATP synthase subunit genes, including ATP5PO (structurally related to ATP5PD), cause variable neurologic phenotypes ranging from hypotonia to epilepsy with developmental delay and movement disorders 4. Additionally, dysregulation of ATP synthase genes occurs in schizophrenia and Alzheimer's disease, suggesting ATP5PD perturbation contributes to neurodegeneration and psychiatric pathology through impaired energy metabolism 56.