Fig 2: mRNA ALPI expression in HEK293T cellsWT ALPI and mutant expression by qRT‐PCR. Data are representative of three experiments and are expressed as mean ± SD.

Fig 3: Colonic inflammation in ALPI‐deficient patients A, BHaematoxylin–eosin staining of colonic biopsies from P1 (A) and P2 (B). Scale bars: 100 μm (A) and 50 μm (B).

Fig 4: WES identification of heterozygous compound mutations in ALPI Variant identification pipeline for WES in P1 and P2 (see also Appendix Tables S1 and S2).Unrelated familial trees showing affected children in black and healthy individuals in white.Sanger sequencing of the region corresponding to mutations in ALPI in both families.Location of ALPI on chromosome 2 and diagrams featuring ALPI gene with its nine exons and ALPI protein with its N‐terminal signal peptide, phosphatase domain and C‐terminal recognition signal for the transamidase complex (GPI‐anchor attachment site), which removes the GPI signal sequence and replaces it by a preformed GPI precursor glycolipid. Arrows point to mutations identified in P1 and P2. Numbers indicate amino acid position.

Fig 5: Loss of function of ALPI mutants A, BAnalysis with ALPI antibody of HEK293T cells (lacking endogenous ALPI expression) after mock transduction or transduction with lentiviral particles encoding indicated mutants. (A) Western blot of whole‐cell lysates. (B) Flow cytometry analysis of surface‐labelled cells.C–E3D modelling of ALPI calculated on the basis of the crystal structure of ALPP. ALPI is represented with one monomer in yellow, and the second in blue. Alanine 350, alanine 360 and catalytic Ser111 are represented in stick in violet, cyan and red, respectively. Deletion of the C‐terminal from Gln439 is shown in pink. Top and bottom views shown in (D) correspond to a 90° rotation.FpNPP phosphatase activity of WT and ALPI mutants measured by the OD405 nm of the reaction supernatants. n = 5, error bars indicate SD. **P = 0.0079, nonparametric, unpaired two‐tailed Mann–Whitney test.GIL‐8 inhibition of LPS‐induced transcription in THP1 cells by WT and ALPI mutants. GAPDH, glyceraldehyde‐3‐phosphate dehydrogenase; EV, empty vector. n = 3, error bars indicate SD. **P = 0.022, nonparametric, unpaired two‐tailed Mann–Whitney test. Source data are available online for this figure.