HCCS (holocytochrome c synthase) is a mitochondrial lyase that catalyzes the covalent attachment of heme to cytochrome c apoprotein, generating mature functional cytochrome c required for electron transport chain activity 1. The enzyme is expressed broadly across tissues with particularly strong expression in heart and skeletal muscle 1. HCCS localizes to the mitochondrial inner membrane where it facilitates critical steps in respiratory electron transport 1. Clinically, HCCS disruption causes microphthalmia with linear skin defects (MLS), an X-linked male-lethal disorder characterized by microphthalmia, corneal opacity, linear skin lesions, and variable neurological and cardiac anomalies 1. Both structural variants (chrX rearrangements and deletions) and intragenic variants have been identified 2. X-inactivation patterns significantly influence phenotypic severity in heterozygous females, with corneal opacity representing the most penetrant feature 2. HCCS should be considered in diagnostic testing for isolated ocular anomalies and congenital aphakia 2. The precise molecular mechanism by which HCCS loss produces MLS remains uncertain, though impaired mitochondrial electron transport is implicated 1.