Apbb1, also known as FE65, is an adaptor protein initially identified as a binding partner of amyloid precursor protein (APP) [2,3]. It contains protein-interaction domains like an N-terminal WW domain and two C-terminal phosphotyrosine-binding (PTB) domains, enabling it to mediate multimolecular complex assembly. Apbb1 is involved in multiple biological processes, including signal transduction during cell stress, protein turnover via the ubiquitin-proteasome system, and various neuronal processes such as neurogenesis and synapse formation [3].

In a study on spermatogonial stem cells (SSCs), Apbb1-/-mice showed disrupted spermatogenesis and reduced fertility. APBB1 was selectively expressed in dormant human SSCs, and its interaction with KAT5 led to GDF15 expression suppression and human SSC proliferation inhibition. Silencing Apbb1 enhanced SSC colonization but impeded differentiation, impairing spermatogenesis. Additionally, 4 deleterious APBB1 mutation sites were found in non-obstructive azoospermia (NOA) patients, and patients with the c.1940C > G mutation had a similar testicular phenotype to Apbb1-/-mice [1].

In conclusion, Apbb1 plays a crucial role in spermatogenesis and male fertility as revealed by the Apbb1-/-mouse model. The discovery of its mutations in NOA patients further emphasizes its importance in male reproductive health, providing potential therapeutic targets for treating male infertility.