Abstract

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 carrier (SLC) group, together with LIMR protein family members. Predicted structures reveal a unique intracellular helix hairpin and a conserved transmembrane core compatible with putative transport activity. This work provides a unifying framework for interpreting the existing evidence on the GPR89 function and proposes that GPR89 should be classified within the LIMR superfamily. © 2025