In this work, we have shown the significant downregulation of RSPO2 (agonist) and SFRP1 (antagonist) in WNT signaling in USP8-mutant corticotropinomas, which supports our hypothesis on the role of USP8-mutation-altered WNT signaling regulation in these tumors. Here, RSPO2 is linked to ACTH-producing pituitary gland adenoma.