Those on the immigration restrictionist side of the debate use the image to symbolize an unruly border, adding guns or nuclear bombs to political cartoons of the sign.
Those who advocate for migrants have redone the sign as a family of pilgrims or college graduates.
"There's only a handful of really iconic images that have been successfully mobilized for the purposes of immigration politics," said Everard Meade, director of the Trans Border Institute at University of San Diego. "The thing with these symbols is that the response is 50-50.
"Some people see that sign and think, 'My God, this is a sign that represents how our immigration policy has just failed, and we've put people in this vulnerable position such that we have to have a road sign so people don't run them over on the highway,'" Meade added.
Others take it as a sign of an out-of-control border, Meade said, and that perception of the image contributed to support for movements like California's Proposition 187, which barred unauthorized immigrants from the public education system and from public health services except for emergency care required by federal law. A federal judge blocked the proposition from taking effect.
Even the sign's disappearance caused split reactions among those involved in immigration political debate.
Joshua Wilson, vice president of the San Diego chapter of the National Border Patrol Council, has supported President Donald Trump's restrictionist policies.
Wilson said he sees not needing the signs anymore as a positive thing. It shows what investing in border security can do, he said.
"I grew up in Los Angeles, and I remember those signs as a kid coming down here," Wilson said. "What it symbolizes to me is how out of control things were before we put in the infrastructure with Operation Gatekeeper."
Operation Gatekeeper, a ramped-up enforcement strategy implemented along the San Diego border in the mid-'90s, shifted migrant routes east over mountains and through deserts.