TET2 (the primary CHIP gene) and other CHIP genes (e.g., DNMT3A, EZF2) act as epigenetic mediators, increasing the likelihood that molecular mechanisms associated with gout involve training phenomena, where external stimuli (in this case, soluble urate) reprogram the epigenome to train the innate immune system to exhibit a heightened response to MSU crystals (Joosten et al., 2020). This evidence concerns the gene STUB1 and gout.