FXYD5 and neoplasm: Calon et al. (2015) demonstrated that poor-prognosis CRC subtypes are primarily defined by stromal gene expression, particularly TGF-β–induced programs in CAFs (Calon et al., 2015). Similarly, Isella et al. (2015) reported that a substantial proportion of the CRC transcriptome originates from stromal cells, correlating with therapeutic failure and adverse outcomes (Isella et al., 2015). Building on this, Lee et al. (2024) showed that dysadherin contributes to ECM remodelling through the MMP9 axis and CAF activation, promoting a more aggressive tumour microenvironment (Lee et al., 2024).