In eukaryotes, the poly(A) tail added at the 3′ end of an mRNA precursor is essential for the regulation ofmRNA stability and the initiation of translation. Poly(A) polymerase (PAP) is the enzyme that catalyzes thepoly(A) addition reaction. Multiple isoforms of PAP have been identified in vertebrates, which originate fromgene duplication, alternative splicing or post-translational modifications. The complexity of PAP isoformssuggests that they might play different roles in the cell. Phylogenetic studies indicate that vertebrate PAPs aregrouped into three clades termed α, β and γ, which originated from two gene duplication events. To date, allthe available PAP structures are from the PAPα clade. Here, we present the crystal structure of the firstrepresentative of the PAPγ clade, human PAPγ bound to cordycepin triphosphate (3′dATP) and Ca2+. Thestructure revealed that PAPγ closely resembles its PAPα ortholog. An analysis of residue conservationreveals a conserved catalytic binding pocket, whereas residues at the surface of the polymerase are moredivergent.