LORICRIN encodes a non-enzymatic structural substrate of cornified-envelope
assembly. The strongest direct evidence comes from biochemical analysis of human
epidermal envelopes and human loricrin, supplemented by mouse loss-of-function and
disease-mutant experiments. The mouse studies establish conserved physiological
consequences but should not be described as direct experiments in human cells.
Two GOA source papers cannot be independently checked for their LORICRIN-specific
experiments from the local cache. The abstract of PMID:10908733 is about SPR1-rich
human oral keratinocyte envelopes and does not mention loricrin; the abstract of
PMID:11698679 is about late envelope proteins and likewise does not mention
loricrin. Both are abstract-only. Their experimental annotations should therefore
be treated with curator deference rather than rejected because the abstracts focus
on other proteins.
The original human characterization recovered loricrin peptides from purified
cell envelopes and directly identified the covalent linkage: PMID:2007607 The same abstract reports that
loricrin is highly insoluble partly because of disulfide bonding and proposes that
its glycine-rich loops contribute flexibility; the latter is a model, not a
separately measured molecular activity.
Peptide sequencing of purified human foreskin epidermal envelopes gives the most
quantitative structural evidence: PMID:7543090 It also recovered links to cytoskeletal components:
PMID:7543090 This supports physical anchoring
and envelope organization, but does not make loricrin a keratin filament protein or
an enzyme.
Recombinant human loricrin and mouse epidermal loricrin were tested as
transglutaminase substrates. The paper states: PMID:7592852 TGase 3 favored intrachain links, whereas TGase 1 favored interchain
oligomers, and the sites used in vitro closely matched those observed in vivo.
Thus peptide cross-linking is a biological process in which loricrin participates;
the catalytic activity belongs to transglutaminases, not loricrin.
Mouse knockout evidence supports a mechanical role but also shows redundancy.
Loricrin contributes about 70% of epidermal-envelope mass in that model and its
loss delayed embryonic barrier formation. Purified knockout envelopes were more
fragile: PMID:11038185
However, the same study reports: PMID:11038185 Increased expression of SPRR
and other envelope components compensated. Consequently, loricrin is a major
structural contributor, but normal steady-state permeability is not an
indispensable, nonredundant output attributable to LORICRIN alone.
Human genetic evidence links an insertional frameshift in the C-terminal
glycine- and glutamine/lysine-rich region to ichthyotic Vohwinkel syndrome:
PMID:8673107 This supports the importance of normal envelope
incorporation but does not by itself define an additional normal molecular
function.
A disease-like mutant in transgenic mice was found in nuclei and cytoplasm rather
than in the envelope: PMID:11038186 Its altered C terminus gained a nuclear-localization signal, and nuclear
deposition disrupted late epidermal differentiation. This is a toxic mutant
gain-of-function mechanism. It must not be used to infer that nuclear localization
or regulation of nuclear processes is a normal core function of wild-type
LORICRIN.