SLC22A10 encodes a member of the solute carrier family 22, classified as an organic anion transporter based on sequence homology 1. However, human SLC22A10 is functionally a unitary pseudogene, inactivated by a fixed missense mutation (P220) that prevents plasma membrane localization 23. In contrast, SLC22A10 orthologs in great apes retain transport function and transport estradiol-17β-glucuronide and conjugated sex hormones with high efficiency (>4-fold accumulation, p<0.001) 23. This functional loss occurred during hominin evolution after divergence from the pan lineage, as Neanderthal and Denisovan genomes retain the ancestral proline 220 sequence 4. Site-directed mutagenesis restoring the leucine at position 220 (P220L) rescues plasma membrane localization and uptake function in human SLC22A10 2. Despite being non-functional in humans, rare variants in SLC22A10 associate with Alzheimer's disease biomarkers reflecting neuronal injury and inflammation 5, and with opioid dependence susceptibility 6. Gene expression is regulated by hepatocyte nuclear factor-1α (HNF-1α) 7, suggesting residual regulatory relevance in humans.