RNA binding proteins bind to RNA in cells to control much of their regulation, such as splicing, stability, transport and translation. RNA binding proteins TDP-43 and FUS/TLS have been previously implicated in ALS and studied. Here we study a closely related family member TAF15 that has also been implicated in ALS. We find similarities between TAF15 and FUS/TLS, but not TDP-43 and identify RNA substrates that are bound and a new motif recognized by TAF15 in mouse brains. Using human IPSC cells from normal and ALS patients, we also identify that TAF15 and FUS affect RNA turnover and have downstream effects on targets resembling ALS FUSR521G mutants and late-stage sporadic ALS patients.