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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, rephasing the ribosome relative to the mRNA. While frameshifting is often employed by viruses, very few phylogenetically conserved examples are known in vertebrate genes and the evidence for some of these is controversial. Here we report a +1 frameshifting signal in the coding sequence of the human gene , encoding the ARL8-dependent, lysosome-kinesin-1 adaptor protein PLEKHM2. This +1 frameshifting signal, UCC_UUU_CGG, is highly conserved in vertebrates and exhibits an influenza virus-like frameshift motif with similar efficiency. 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.