In cells derived from palmoplantar keratoderma patients harboring the CK1α-binding-deficient SACK1G<sup>R265P</sup> mutation, DEG-77 targets CK1α and mitotic SACK1D but not SACK1G<sup>R265P</sup>, highlighting the requirement for CK1α-SACK1 interaction to achieve codegradation. This evidence concerns the gene CSNK1A1 and hereditary palmoplantar keratoderma.