biostudies-literatureUnknown27Quercia-Raty CAAlso called the Golgi pH regulator (GPHR), GPR89 is an orphan membrane protein found in nearly all eukaryotic lineages. Despite its broad phylogenetic distribution, the evolutionary history, structural diversity, and function of GPR89 remain poorly understood. In this study, we present a comprehensive bioinformatic analysis of GPR89 in Eukarya by integrating phylogenetic reconstruction, genomic synteny, sequence conservation, and structural modeling. While GPR89 is typically encoded as a single-copy gene, we identified lineage-specific duplications in both vertebrates and vascular plants. In contrast to the large sequence conservation, differences can be observed in whether plants and animals preserve the gene structure flanking GPR89. Structural clustering places GPR89 within the solute cComputational and structural biotechnology journal4846-4855https://www.ebi.ac.uk/biostudies/studies/S-EPMC12639261biostudies-literatureEvolutionary and structural bioinformatics identifies GPR89 as a conserved member of the LIMR protein superfamily.PMC12639261Robeson LQuercia-Raty CABrauchi SEfalseEvolutionary and structural bioinformatics identifies GPR89 as a conserved member of the LIMR protein superfamily.Also called the Golgi pH regulator (GPHR), GPR89 is an orphan membrane protein found in nearly all eukaryotic lineages. Despite its broad phylogenetic distribution, the evolutionary history, structural diversity, and function of GPR89 remain poorly understood. In this study, we present a comprehensive bioinformatic analysis of GPR89 in Eukarya by integrating phylogenetic reconstruction, genomic synteny, sequence conservation, and structural modeling. While GPR89 is typically encoded as a single-copy gene, we identified lineage-specific duplications in both vertebrates and vascular plants. In contrast to the large sequence conservation, differences can be observed in whether plants and animals preserve the gene structure flanking GPR89. Structural clustering places GPR89 within the solute c2025-01-01T00:00:00Z20252026-06-06T07:04:57.756Z2026-06-06T03:07:02.082ZS-EPMC126392614128241610.1016/j.csbj.2025.11.003