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Programmed ribosomal frameshifting is a translational recoding phenomenon in which a proportion of ribosomes are stimulated to slip backwards or forwards on an mRNA 1 , rephasing the ribosome relative to the mRNA. While frameshifting is often employed by viruses 2 , very few phylogenetically conserved examples are known in vertebrate genes and the evidence for some of these is controversial 3,4 . Here we report a +1 frameshifting signal in the coding sequence of the human gene PLEKHM2 , encoding the ARL8-dependent, lysosome-kinesin-1 adaptor protein PLEKHM2 5 . This +1 frameshifting signal, UCC_UUU_CGG, is highly conserved in vertebrates and exhibits an influenza virus-like frameshift motif with similar efficiency 6,7 . Purification and mass spectrometry of GFP-tagged trans-frame protein from cells confirms frameshifting. Structure prediction shows that the new C-terminal domain generated by this frameshift forms an alpha-helix. This additional domain relieves PLEKHM2 from autoinhibition, allowing it to move to the tips of cells via association with kinesin-1 without requiring activation by ARL8. Thus, the frameshift proteoform generates a constitutively active adaptor of kinesin-1.