RPS4Y2 is a Y chrY-linked ribosomal protein gene that serves as a structural constituent of the cytosolic small ribosomal subunit and plays a role in protein translation 1. Unlike its ubiquitously expressed X-linked homologue RPS4X, RPS4Y2 exhibits testis-specific and prostate-restricted expression patterns 1. The gene arose through duplication from RPS4Y1 approximately 35 million years ago after the divergence of New World monkeys 2. Evolutionary analysis reveals that RPS4Y2 has been under positive selection in the human lineage, representing the first evidence of positive selection acting on a ribosomal protein gene 2. Despite accumulating amino acid changes since duplication, RPS4Y2 maintains a structurally conserved three-dimensional architecture with novel C-terminal features that may indicate functional specialization in spermatogenesis 1. The protein shows higher expression in testis biopsies containing germ cells and may be important for germ cell development 1. RPS4Y2 has been identified as a hub gene in allergic rhinitis networks 3 and as a potential biomarker for metabolic-associated fatty liver disease subtypes 4, though its primary function remains centered on male fertility and spermatogenesis.