This strategy of “NAAIRS” cassette substitutions was chosen due to prediction of this motif being tolerated in the three-dimensional structure of proteins [26], prior use of this approach in mapping functional regions of both retinoblastoma and the telomerase catalytic subunit [27,28], and our previous success employing this strategy to identify Gα12 determinants of binding to the scaffolding subunit of protein phosphatase-2A and the cytoplasmic tail of polycystin-1 [29,30]. The gene discussed is PKD1; the disease is retinoblastoma.