Lysosome-Related Organelle Biogenesis and Transport Module

This is a shared mechanism module, not a disease. Disorder-specific substitutions at the trigger node, grouped by which step of the melanosome life cycle the lost component serves: 1. Cargo delivery during biogenesis - the BLOC-1, BLOC-2 and BLOC-3 complexes and adaptor protein complex AP-3 (Hermansky-Pudlak syndrome, HPS1-HPS11). Melanogenic enzymes and structural cargo are not routed into the maturing melanosome, so the organelle forms but is not properly loaded. 2. Organelle size and fission control - LYST (Chediak-Higashi syndrome). The giant inclusion bodies that are the diagnostic hallmark are LROs that have failed to be resolved into normal-sized organelles, and cargo is mis-sorted into them. 3. Peripheral capture and positioning - the RAB27A-melanophilin-myosin Va tripartite complex (Griscelli syndrome types 2, 3 and 1 respectively). The melanosome is built and pigmented normally but is never tethered at the dendrite tip for transfer. Curate the specific step; do not describe all three as "defective melanosome biogenesis", which is true only of the first. **Critical negative boundary: oculocutaneous albinism does NOT conform.** In OCA the lesion is in melanin *synthesis* (TYR, TYRP1, OCA2, SLC45A2) - the melanosome and its trafficking machinery are intact and the organelle is simply empty. Here the opposite holds: pigment is synthesized and retained, so affected melanocytes are *more* densely pigmented than normal while the skin is less so. That inversion, visible on skin histology as melanin-distended melanocytes beside melanin-free keratinocytes, is the single most useful discriminator and the reason this module and the albinism mechanism must not be merged. A disorder whose hypopigmentation comes from absent melanin synthesis does not conform no matter how similar the clinical picture. Distinct from `lysosomal_substrate_accumulation`. That module models the conventional lysosome failing to degrade what it receives; this one models specialized lysosome-*related* organelles failing to be built, sized, or positioned. A conforming entry here has no storage material and no hydrolase deficiency. Not an Xogenesis module: the terminal output is the failure of a normal delivery process, not the formation of a pathological anatomical entity. The Chediak-Higashi giant granule is the one arguable exception - it is a new, pathological structure - but it is an intermediate in this chain rather than its endpoint, and it is a malformed normal organelle rather than a derived new formation, so no anchor stanza is asserted. Conformance requires evidencing a trafficking or biogenesis lesion in the LRO machinery. Hypopigmentation alone, or expression of an LRO gene in melanocytes, is not sufficient. **Attachment points differ, and the difference is informative.** Only the Griscelli route conforms at the central effector, because only there is the melanosome fully built and pigmented and simply never delivered. In Hermansky-Pudlak syndrome the melanosome *is* transferred - it is merely under-loaded, so melanin production itself is reduced - and the entry therefore conforms at the trigger, the melanosome arm and the other-LRO arm but NOT at the delivery node. Chediak-Higashi sits between the two: its giant melanosomes are abnormally distributed and transfer poorly, and its entry attaches at the melanosome arm. Do not "tidy" these into uniform conformance at the central effector; the disagreement is a real statement about where each disorder's pigmentary failure lies, and flattening it would assert something the evidence does not support.