Impaired XBP1 splicing downstream of SRP54 mutations. During physiological conditions (A), the signal recognition particle 54 (SRP54) facilitates the translocation of the ribosome-associated unspliced XBP1 (XBP1u) to the ER where it is spliced (XBP1s). In pathological conditions (B), SRP54 mutations found in patients act in a dominant-negative manner to wild-type (WT) SRP54 and impair XBP1 splicing, leading to neutropenia and decreased size of the exocrine pancreas. Image by Veronica Bergo, created with BioRender.com.