Fig 2: TTC36 deficiency in mice results in impaired learning and memory. a Mean escape latency per training block for the aged wild-type and Ttc36−/− mice (8–12 months, WT group: n = 13, Ttc36−/− group: n = 11), Mean ± s.e.m. b Mean escape latency for the aged wild-type and Ttc36−/− mice (8–12 months, WT group: n = 13, Ttc36−/− group: n = 10) during retention probe trial, Mean ± s.e.m. c Nest construction was quantified in aged wild-type and Ttc36−/−mice (8–12 months, WT group: n = 14, Ttc36−/− group: n = 7) mice. Data from panels a and c are analyzed by two-way ANOVA with Sidak’s post-hoc test. **P < 0.01. d Schematic for HPD degradation regulated by the TTC36-STK33-PELI1 signaling axis in tyrosinemia, inducing neurological damage and disorders

Fig 3: PELI1 binds to phosphorylated T382 of HPD. Immunoblotting analyses were performed with the indicated antibodies a–f. a HEK293T cells were transfected with the indicated plasmids. MG-132 (10 μM) was added into the culture medium of the cells 12 h before they were harvested. The cell lysates were treated with or without calf intestinal alkaline phosphatase (CIP) (1 unit CIP per µg of protein). A Ni-NTA pull-down assay was performed. b HEK293T cells were transfected with indicated plasmids. Immunoprecipitation with an anti-Flag antibody was performed. c WT Flag-PELI1 or Flag-PELI1 R104A was expressed in HEK293T cells expressing HA-Ub and His-HPD. MG-132 (10 μM) was added to the cells 12 h before they were harvested with a guanidine–HCl-containing buffer. A Ni-NTA pull-down assay was performed. d LO2 cells expressing Peli1 shRNA were reconstituted with expression of RNAi-resistant WT PELI1 or PELI1 R104A. e HEK293T cells were transfected with indicated plasmids. Immunoprecipitation with anti-Flag antibody was performed. f His-HPD WT or His-HPD T382A were expressed in HEK293T cells expressing HA-Ub, with or without reconstituted expression of Flag-PELI1. MG-132 (10 μM) was added to the cells 12 h before they were harvested with a guanidine–HCl-containing buffer. A Ni-NTA pull-down assay was performed