EIF1AY encodes eukaryotic translation initiation factor 1A Y-linked, a component of the 43S pre-initiation complex essential for translation initiation. The protein binds to mRNA cap-proximal regions, facilitates 5'-UTR scanning, and promotes start codon recognition 1. EIF1AY coordinates with EIF1 and EIF5B to assemble the 48S complex at the initiation codon and orient the initiator methionine-tRNA for 60S ribosomal subunit joining to form the 80S initiation complex. The protein is released after 80S complex formation, positioning its globular domain in the 40S ribosomal A site. EIF1AY shows notably elevated expression in male heart tissue compared to female tissue, driven by evolutionary loss of a Y-linked microRNA target site that allows preferential upregulation of EIF1AY over its X-linked homolog EIF1AX 1. This sex-biased expression results in translation initiation factor abundance nearly twice higher in male hearts, representing a dosage-sensitive, tissue-specific difference. Disease relevance includes associations with cardiovascular conditions—EIF1AY was identified as a hub gene in non-STEMI patients 2 and appears among heart failure-associated targets 3. In urothelial carcinoma, EIF1AY is significantly upregulated in tumor cytoplasm 4, and it serves as a tertiary lymphoid structure-associated gene in pancreatic cancer prognostication 5, 6. EIF1AY also functions as a Y-chromosome Y marker for identifying donor-derived cells in transplantation studies 7.