Exploring QRICH2 interactome to understand its role in sperm flagellar assembly and function

Male infertility affects approximately 7% of men worldwide, with Multiple Morphological Abnormalities of the Flagella (MMAF) representing one of its most severe forms. QRICH2 has been identified as a key gene in MMAF pathogenesis, yet its protein–protein interaction network remains virtually uncharacterized. Using Yeast Two-Hybrid (Y2H) high-throughput screening of the QRICH2 C-terminal fragment, 199 candidate interactors were identified, including flagellar cytoskeletal proteins, gene expression regulators, and ubiquitin-proteasome components. Among these, 24 showed testis-enriched expression and 48 were recurrently identified, marking them as high-confidence candidates. Of the 20 most relevant hits selected for binary validation by Gaussia princeps Complementation Assay (GPCA), 12 produced a positive signal. Screening of the two remaining fragments is ongoing and will enable broad coverage of QRICH2's full-length interactome.