ZFAND6 (zinc finger AN1-type containing 6) is a multifunctional protein with roles in immune regulation, apoptosis, and peroxisomal protein trafficking. In immune signaling, ZFAND6 modulates TNF-induced NF-κB activation by regulating Lys-48-linked polyubiquitination of TRAF2 and reducing its association with RIPK1, thereby negatively regulating apoptosis [UniProt]. In peroxisomal biology, ZFAND6 functions as a cofactor for Pex6 AAA-ATPase in PTS1-receptor recycling, with its A20 zinc-finger domain preferentially binding cysteine-ubiquitinated Pex5; this activity is essential for peroxisomal protein import and Pex5 stability 1. Beyond these canonical functions, ZFAND6 has emerging disease associations. Genetic variants (rs11634397) show associations with type 2 diabetes risk across multiple populations, with heterozygous genotypes conferring reduced prediabetes susceptibility in Saudi cohorts and homozygous variants showing increased risk in Indian populations 23. CircRNA-ZFAND6 is downregulated in unexplained recurrent spontaneous abortion and promotes trophoblast proliferation while suppressing mitochondrial apoptosis through a ceRNA mechanism involving miR-575 and SOD2 4. Additionally, ZFAND6 expression is reduced in infertile males and involved in alternative splicing regulation during interferon-mediated antiviral responses 56.