Biogenesis of lysosome-related organelles complex 1(BLOC1)is composed of eight distinct proteins.Loss-of-function of its subunits DTNBP1,BLOC1S3 and PLDN,leads to three representative subtypes of Hermansky-Pudlak syndrome(HPS),a human autosomal recessive disorder characterized by oculocutaneous albinism and platelet storage pool deficiency that are resulted from defective biogenesis of tissue-specific lysosome-related organelles.Additionally,two HPS models for subunits MUTED and CNO have also been established in mouse.However,the loss of remaining three components(BLOC1S1,BLOC1S2 or SNAPIN)is embryonically lethal in mouse,implying potential novel functions beyond BLOC1.Here,we generated a zebrafish line of BLOC1S1 deficiency using the CRISPR/Cas9 System.Mutant larvae displayed multi-systemic defects including reduced level of melanin,lack of light reflections from iridophores,deflated swim bladder,hepatomegaly and progressive liver necrosis.The melanosomes in mutants contained many vesicle-like structures,which is a feature of immature melanosome; moreover,iridosomes are completely absent from the mutants.These results suggest that the maturation/biogenesis of these pigment granules is blocked when BLOC1S1 was knocked out.We also found that the formation and organization of three tissue layers in swim bladder is not affected,but the swim bladder in BLOC1S1 mutant contained more lamellar body-like organelles.Lamellar body is a kind of lysosome-related organelles and presented in alveolar epithelium type Ⅱ cell in mammals.Lamellar body mainly functions in storing and secreting lung surfactant phospholipid,which is essential for normal lung function and exhibits an anti-adhesive role in both mammals and non-mammals.We hence examined the surfactant system in the mutant.Notably,oil-red staining indicated that the surfactant system is invisible after BLOC1S1 deletion,suggesting that the maturation and/or secretion pathways of lamellar body are impaired,thus resulting in defective surfactant formation and finally swim bladder inflation.In summary,we have established a novel model for HPS in zebrafish,and explored the essential role of BLOC1S1 in surfactant formation,which might contribute to,at least partially,the lethal phenotype in mammals.