Moreover, a gain in RSPO2 or RSPO3 levels is evident in a subpopulation of colorectal cancer patients, caused either by stromal overexpression or by specific gene fusions, among which EIF3E–RSPO2 and PTPRK–RSPO3 occur mutually exclusively with classical APC and CTNNB1 driver mutations [7, 8, 9, 10, 11, 12, 13]. Here, RSPO2 is linked to colorectal cancer.