Background: In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis. RPE65 is suspected to be involved in cellular uptake of retinol which is transported in the bloodstream complexed with plasma retinol-binding protein. Objectives: To evaluate protein and mRNA expression of RPE65 in actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) compared with normal skin. Methods: RPE65 mRNA expression in skin tumours relative to normal skin of the respective donor was studied by real-time polymerase chain reaction in AK (n=15), invasive SCC (n=30) and BCC (n=18). A peptide-specific anti-RPE65 a ntibody was used for immunohistochemical staining of formalin-fixed and paraffi n-embedded tissue sections of the respective tumours. Results: RPE65 mRNA expre ssion was reduced in AK. A highly significant reduction of RPE65 mRNA was observ ed in invasive SCC relative to normal skin of the respective donors. Immunohisto chemistry revealed a continuous staining of basal and suprabasal keratinocytes i n normal human epidermis. RPE65 in AK shown by immunohistochemical staining was reduced and quite irregular, whereas invasive SCC revealed no staining of tumour cells with the anti-RPE65 antibody. RPE65 mRNA values were elevated, whereas i mmunohistochemical staining for RPE65 proteinwas heterogeneous in BCC. Conclusio ns: These results suggest progressive downregulation of RPE65 from AK to invasive SCC. Background: In a recent report we described RPE65, a protein originally characterized in retinal pigment epithelium, to be expressed in normal human epidermis. RPE65 is suspected to be involved in cellular uptake of retinol which is transported in the bloodstream complexed with plasma retinol-binding protein. Objectives: To evaluate protein and mRNA expression of RPE65 in actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) compared with normal skin. Methods: RPE65 mRNA expression in skin tumours relative to normal skin of the peptides were assayed by real-time polymerase chain reaction in AK (n = 15), invasive SCC (n = 30) and BCC (n = 18). A peptide-specific anti-RPE65 a ntibody was used for immunohistochemical staining of Results: RPE65 mRNA expre ssion was reduced in AK. A highly significant reduction of RPE65 mRNA was observed in invasive SCC relative to normal skin o Immunohisto chemistry revealed a continuous staining of basal and suprabasal keratinocytes in normal human epidermis. RPE65 in AK shown by immunohistochemical staining was reduced and quite irregular, whereas invasive SCC revealed no staining of tumor cells with the anti-RPE65 antibody. RPE65 mRNA values ​​were elevated, and i mmunohistochemical staining for RPE65 protein was heterogeneous in BCC. Conclusio ns: These results suggest progressive downregulation of RPE65 from AK to invasive SCC.