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TTLL

TTLL, short for tubulin tyrosine ligase-like, refers to a family of enzymes that catalyze the post-translational modification of tubulin by polyglutamylation. Members of the TTLL family share a conserved catalytic domain related to tubulin tyrosine ligase but differ in tissue distribution and substrate preferences. In humans, several TTLL paralogs have been described, including TTLL1, TTLL4, TTLL5, TTLL6 and TTLL9, among others.

These enzymes act on alpha- and/or beta-tubulin within microtubules, adding glutamate residues to create polyglutamate side

The TTLL gene family is conserved across eukaryotes and comprises multiple paralogs with distinct or overlapping

Clinical and research interest in TTLL enzymes centers on how altered polyglutamylation affects development and disease.

chains.
Polyglutamylation
modulates
microtubule
properties
by
influencing
the
binding
of
microtubule-associated
proteins
and
motor
proteins,
which
in
turn
can
affect
microtubule
stability,
intracellular
transport,
and
mitotic
processes.
TTLL
enzymes
thus
play
roles
in
a
range
of
cellular
activities,
from
neuronal
function
to
ciliogenesis.
tissue
expression
and
substrate
specificity.
The
exact
pattern
of
activity
can
vary
among
organisms
and
cell
types,
making
TTLLs
a
focus
of
studies
on
microtubule
regulation
and
its
impact
on
cell
biology.
Dysregulation
of
TTLL
activity
has
been
linked
to
defects
in
ciliary
function
and
neurodevelopment
in
model
organisms,
and
ongoing
work
aims
to
clarify
their
roles
in
human
health
and
disease.