Indeed, while SM04690 has been used in a localized fashion to treat osteoarthritis of the knee (Yazici et al., 2020; Tambiah et al., 2021), our work suggests that the use of broad-acting modulators of alternative splicing should be met with caution, as inhibition of the CLK family of kinases induces alternative splicing in many transcripts (Araki et al., 2015), which may lead to undesired off-target effects. Here, CLK1 is linked to osteoarthritis.