The effect of some variants of the CASP10 and PIK3CD genes, found in patients showing symptoms and laboratory alterations similar to ALPS patients (the so-called ALPS undefined, or ALPS-U), but not fully matching the 2009 NIH revised diagnostic criteria [11], was investigated through proper functional tests, allowing confirmation of their postulated pathogenicity [34,44,45]. The gene discussed is PIK3CD; the disease is autoimmune lymphoproliferative syndrome.