Zzef1, the ZZ-type zinc finger and EF-hand domain protein 1, is a multidomain-containing protein. It functions as a histone H3 reader, with its second ZZ domain (ZZEF1ZZ2) binding to the N-terminus of histone H3 and accommodating common epigenetic marks on the H3 tail. It also serves as a transcriptional coregulator of Krüppel-like factors, physically interacting with KLF9 and KLF6 to regulate a common set of target genes [1].

In a family with autosomal-dominant macular dystrophy, a 560 kb tandem duplication on chromosome 17 led to the formation of a novel ZZEF1-ALOX15 fusion gene. Functional studies showed that this fusion gene, driven by the ZZEF1 promoter, caused mislocalization and overexpression of ALOX15, resulting in retinal disorganization, photoreceptor, and RPE damage [2]. In pigs, in the Yorkshire breed genome, ZZEF1 was associated with NBA and TNB traits, which are related to reproductive performance [3].

In conclusion, Zzef1 has diverse functions including histone reading and transcriptional coregulation. Its involvement in macular dystrophy in humans and reproductive performance in pigs showcases its significance in different biological processes and disease areas. Research on Zzef1, especially through gene-related models, helps to understand its roles in these contexts.